Open AccessNitric oxide and prostaglandins – important players in endothelin-1 induced myocardial distensibility
Author(s) -
Carmen Brás-Silva,
D. MonteiroSousa,
Ana Joana Duarte,
Marina Prista Guerra,
Ana Patrícia Fontes-Sousa,
Carla Pinto Moura,
José Carlos Areias,
Adelino LeiteMoreira
Publication year - 2008
Publication title -
physiological research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.647
H-Index - 70
eISSN - 1802-9973
pISSN - 0862-8408
DOI - 10.33549/physiolres.931148
Subject(s) - lusitropy , medicine , endocrinology , chemistry , nitric oxide , endothelin receptor , inotrope , nitric oxide synthase , saline , endothelin 1 , prostaglandin , cyclooxygenase , diastole , blood pressure , enzyme , receptor , biochemistry
This study investigated whether endothelin (ET)-1-inducedincrease in myocardial distensibility is preserved in heart failure(HF) and whether it is modulated by nitric oxide (NO) andprostaglandins. New Zealand white rabbits were treated withdoxorubicin (1 mg/kg, intravenously twice a week for 8 weeks,DOX-HF group) or saline (control group). Effects of ET-1 (0.1, 1,10 nM) were tested in papillary muscles from the DOX-HF groupand a control group in the presence of: i) intact endocardialendothelium (EE); ii) damaged EE; iii) NG -nitro-L-arginine (L-NNA; NO synthase inhibitor), and iv) indomethacin (INDO;cyclooxygenase inhibitor). In the presence of an intact EE, ET-1promoted concentration-dependent positive inotropic andlusitropic effects that were maintained after damaging the EE, inthe presence of L-NNA or INDO and in the DOX-HF Group. ET-1reduced resting tension at the end of the isometric twitch(increased diastolic distensibility) by 3.2±1.3 %, 6.0±1.6 % and8.8±2.7 % (at 0.1, 1 and 10 nM, respectively), in muscles withintact EE, effect that was completely abolished after damagingEE, in the presence of L-NNA or INDO or in the DOX-HF Group.This study demonstrated that the increase in myocardialdistensibility induced by ET-1 is absent in HF and is dependent ofNO and prostaglandin release.